Probability Of Tumor Progression Research Articles

Catalytic activity of serum and immunoglobulins of classes G and A in patients with breast cancer

The objective of this study was to investigate DNase, various types of proteolytic and oxidoreductase serum and abzyme activities, as well as the serum contents of free DNA in patients with breast tumors in accordance with the clinical, pathological and immunohistochemical characteristics of the tumors. It was found that catalytic antibodies isolated from blood serum of patients with breast oncopathology exhibit proteolytic, DNase and oxidoreductase activity, which varies depending on the course of the disease. It is worth noting that catalytic activity of IgAs (per unit of Ig concentration) can be 1-2 orders of magnitude higher than the analogous activity of IgGs. It was found that DNase, proteolytic (cathepsin G, cathepsin B) serum enzymatic activities and cathepsin G-like activity of IgG and IgA differ in patients with malignant and benign breast tumors and in healthy individuals. These parameters depend on the advance of the tumor process, histological and immunohistochemical characteristics of the tumor, as well as on the probability of tumor progression. In particular, the progression of the tumor process is accompanied by an increase of the activity of serum DNase and cathepsin B, decline of the concentration of patients` serum DNA, being also followed by marked changes of the nuclease, proteolytic and oxidoreductase activity of IgG and IgA.

Clinicopathological and Molecular Prognostic Classifier for Intermediate/High-Risk Clear Cell Renal Cell Carcinoma

Simple SummaryIn this report, we identified biomarkers for tumor progression from tissue samples of intermediate/high-risk ccRCC. Using the molecular findings and the clinical data, we developed an improved prognostic model which could help to provide better individualized management recommendations.The probability of tumor progression in intermediate/high-risk clear cell renal cell carcinoma (ccRCC) is highly variable, underlining the lack of predictive accuracy of the current clinicopathological factors. To develop an accurate prognostic classifier for these patients, we analyzed global gene expression patterns in 13 tissue samples from progressive and non-progressive ccRCC using Illumina Hi-seq 4000. Expression levels of 22 selected differentially expressed genes (DEG) were assessed by nCounter analysis in an independent series of 71 ccRCCs. A clinicopathological-molecular model for predicting tumor progression was developed and in silico validated in a total of 202 ccRCC patients using the TCGA cohort. A total of 1202 DEGs were found between progressive and non-progressive intermediate/high-risk ccRCC in RNAseq analysis, and seven of the 22 DEGs selected were validated by nCounter. Expression of HS6ST2, pT stage, tumor size, and ISUP grade were found to be independent prognostic factors for tumor progression. A risk score generated using these variables was able to distinguish patients at higher risk of tumor progression (HR 7.27; p < 0.001), consistent with the results obtained from the TCGA cohort (HR 2.74; p < 0.002). In summary, a combined prognostic algorithm was successfully developed and validated. This model may aid physicians to select high-risk patients for adjuvant therapy.

Pituitary adenomas in the setting of multiple endocrine neoplasia type 1: a single-institution experience.

Multiple endocrine neoplasia type 1 (MEN1) is a rare, autosomal-dominant tumor disorder characterized by the development of pituitary tumors and other endocrine neoplasms. Diagnosis is made clinically based on the development of 2 or more canonical lesions (parathyroid gland, anterior pituitary, and enteropancreatic tumors) or in family members of a patient with a clinical diagnosis of MEN1 and the occurrence of one of the MEN1-associated tumors. The goal of this study was to characterize pituitary tumors arising in the setting of MEN1 at a single institution. The probability of tumor progression and the likelihood of surgical intervention in patients with asymptomatic nonfunctional pituitary adenomas were also analyzed. A retrospective review of a prospectively maintained institutional database was performed for patients with MEN1 diagnosed from 1970 to 2017. Data included patient demographics, tumor characteristics, treatment strategies, and outcomes. A review of the database identified 268 patients diagnosed with MEN1, of whom 158 (59%) were female. Among the 268 patients, 139 (51.8%) had pituitary adenomas. There was a higher prevalence in women than in men (65% vs 35%, p < 0.005). Functional adenomas (57%) were more common. Prolactin-secreting adenomas were the most common functional tumors. Macroadenomas were seen in 27% of patients and were more likely to be symptomatic and locally aggressive (p < 0.001). Forty-nine patients (35%) underwent transsphenoidal resection at some point during their disease course. In 52 patients who were initially observed with MEN1 asymptomatic nonfunctional adenomas, only 5 (10%) progressed to need surgery. In MEN1 patients, an initial parathyroid lesion is most likely followed in order by pituitary, pancreatic, adrenal, and, finally, rare carcinoid tumors. Asymptomatic nonfunctional pituitary adenomas in patients with MEN1 may be followed safely with MRI. In this series, parathyroid tumors developed at the lowest median age of all cardinal tumors, and development of additional cardinal MEN1 lesions followed a predictable pattern. This pattern of disease progression could have significant implications for disease surveillance in clinical practice and may help to target clinical resources to the lesions most likely to develop next. This may aid with early detection and treatment and warrants further study.

Establishment of risk model for predicting the progression within 1 year of patients with gastric neuroendocrine neoplasms and its value of prediction

To establish the risk model for predicting the progression within 1 year of patients with gastric neuroendocrine neoplasms(gNEN) and to evaluate its value of prediction. Clinical data of 127 gENE patients with histologically comfirmed sporadic gNEN from January 1999 to February 2015 in Nanfang Hospital of Southern Medical University(n=63) and The First Affiliated Hospital of Sun Yat-sen University(n=64) were collected retrospectively. Twenty-five patients without follow-up were excluded, so a total of 102 cases were enrolled in the analysis. Tumor size enlargement, lesion number increase, recurrence after resection of primary tumor and emergence of tumor metastasis were defined as tumor progression. Patients were divided into progression group (above definitions occurred within 1 year, n=56) and non-progression group (above definitions did not occur within 1 year, n=46). Logistic regression analysis was used to identify the influencing factors of progression within 1 year and the regression equation was acquired, then the probability of progression within 1 year of gNEN patients was obtained to predict the grading: grade I(: the probability of tumor progression within 1 year was < 25.0%; grade II(: this probability was from ≥25.0% to <50.0%; grade III(: this probability was from ≥50.0% to <75.0%; grade IIII(:this probability was ≥75.0%. Spearman correlation analysis was used to study the correlation between predictive grading and the occurrence of disease progression in patients with gNEN NET within 1 years. The ROC curve of different prediction methods was drawn, then the area under the curve(AUC), sensitivity and specificity were calculated and compared. Multivariate regression analysis showed that tumor size(OR=1.048, 95%CI:1.014-1.083, P=0.005), Ki-67 index(OR=2.045, 95%CI:1.261-3.316, P=0.004), and surgical resection of the primary lesion(OR=0.074, 95%CI:0.011-0.497, P=0.070) were independent influencing factors of the progression of gNET within 1 year. The regression equation was as below: P(Y)=1/[1+ e -(-0.934+0.047a+0.715b-2.597c)]. (a: tumor size, b: Ki-67 grading, c: undergoing the surgical resection of the primary lesion). Prediction grading was based on regression equation: 28 cases (29.2%) belonged to grade I(, 9 cases (9.4%) to grade II(, 24 cases (25.0%) to grade III(, and 35 cases (36.5%) to grade IIII(. The probability of progression within 1 year of patients in grade I(, II(, III( and IIII( was 10.7% (3/28),5/9, 58.3%(14/24), and 91.4%(32/35) respectively, with significant difference (χ2=41.236, P=0.000). Prediction grading was positively correlated with the occurrence of tumor progression in gNEN patients within 1 year(r=0.644, P=0.000). The AUC of prediction grading to predict the progression of gNEN within 1 year was 0.857, while the sensitivity was 85.2% and the specificity was 69.0%. DeLong method was used to compare the AUC values of prediction grading, Ki-67 grading and TNM staging. Comparison result revealed that the predictive value of prediction grading was not significantly different with that of TNM staging (P=0.303), but was better than that of Ki-67 grading (P=0.006). Our grading standard can objectively and accurately reflect the probability of progression within one year in gNEN patients. The later the grading, the higher the probability of progression within 1 year is for gNEN patients.

Genetic alterations of HER genes in chromophobe renal cell carcinoma

Chromophobe (ch) renal cell carcinoma (RCC) is the 3rd most common subtype of RCC and occurs in 5% of all RCCs. Although chRCC generally demonstrates more favorable outcomes compared with other subtypes of RCC, there is a 6-7% probability of tumor progression and metastasis in this disease. The subclassification of a more aggressive subtype of chRCC may be useful for the management of this cancer. The Erb-B2 receptor tyrosine kinase 2 [also known as human epidermal growth factor receptor (HER) 2] gene has been reported to be important in chRCC. The present study aimed to further investigate the abnormalities of the HER family genes and their potential association with chRCC. Fluorescence in situ hybridization was performed on 11 chRCC tissue specimens, and the Spearman's rank correlation coefficient analysis was used to assess the results. The loss of one copy of the HER2 and HER4 genes was observed to be the major alteration of the tumor cells in all chRCC cases. Statistical data indicated that loss of the HER2 gene was strongly correlated with loss of the HER4 gene (P=0.019). The findings of previous studies were also combined for analysis, and were consistent with those of the present study. In addition, the amplification of HER1 was also strongly correlated with the amplification of HER4 (P=0.004). Furthermore, a high percentage of genetic structural rearrangements was observed in HER3 genes, which was significantly associated with amplification of HER2 (P=0.005). Certain alterations in the HER gene family were also noted as a phenomenom in chRCC. Therefore, the characterization of the underlying aberrant functions of HER genes may be of interest for additional studies in the context of using HER genes to distinguish between RCC subtypes in order to establish improved treatment guidelines.

Residual nonfunctioning pituitary adenomas: prognostic value of MIB-1 labeling index for tumor progression

In residual nonfunctioning pituitary adenomas, reliable prognostic parameters indicating probability of tumor progression are needed. The Ki 67 expression/MIB-1 labeling index (LI) is considered to be a promising candidate factor. The aim in the present study was to analyze the clinical usefulness of MIB-1 LI for prognosis of tumor progression. The authors studied a cohort of 92 patients with nonfunctioning pituitary adenomas. Based on sequential postoperative MR images, patients were classified as tumor free (51 patients) or as harboring residual tumor (41 individuals). The residual tumor group was further subdivided in groups with stable residual tumors (14 patients) or progressive residual tumors (27 patients). The MIB-1 LI was assessed in tumor specimens obtained in all patients, and statistical comparisons of MIB-1 LI of the various subgroups were performed. The authors found no significant difference of MIB-1 LI in the residual tumor group compared with the tumor-free group. However, MIB-1 LI was significantly higher in the progressive residual tumor group, compared with the stable residual tumor group. Additionally, the time period to second surgery was significantly shorter in residual adenomas showing an MIB-1 LI>3%. The data indicate that MIB-1 LI in nonfunctioning pituitary adenomas is a clinically useful prognostic parameter indicating probability of progression of postoperative tumor remnants. The MIB-1 LI may be helpful in decisions of postoperative disease management (for example, frequency of radiographic intervals, planning for reoperation, radiotherapy, and/or radiosurgery).

W1775 Significance of Perihepatic Lymphadenopathy in Patients with Cirrhosis Undergoing Liver Transplantation

Background: While 5 year survival and tumor progression after radiofrequency ablation (RFA) and transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) have been studied, data on cost-effectiveness (CE) comparing these 2 procedures are lacking. Using Markov models, we assessed whether RFA or TACE was more costeffective. Methods: Clinical and financial data were obtained for RFA or TACE patients from June 2006 June 2008. Patient's age, gender, tumor size, treatment course, and direct costs were recorded. Costs of complications were excluded when entering direct procedure costs into the model. Probabilities of tumor progression after RFA or TACE were obtained from published studies. Data was analyzed using TreeAge Pro 2008 Suite 1.2 (TreeAge Software Inc, Williamstown, MA). A Markov model was developed to compare costs and survival outcomes over 5 years, and sensitivity analyses assessed whether model results were stable within plausible ranges of the estimated components. Results: 95 patients were evaluated, 16 received RFA (age = 62.5 ± 11.4 yrs; 10M), and 79 received TACE (age = 64.4 ± 10.6 yrs; 58M). Average tumor size for RFA was 2.23 x 1.84 cm ± 0.96 x 0.83 cm, while for TACE was 3.02 x 2.43 cm ± 1.38 x 1.31 cm. The baseline estimate of the probability of tumor progression after RFA was 0.056 (range = 0.036-0.06) and with TACE was 0.43 (range = 0.19-0.68). Average cost of RFA is $3133 (range=$1760 to $8063) while TACE is $6828 (range=$6687 to $7132). The incremental cost-effectiveness ratio average is $2908 (range= $2086 to $3730). Over 5 years, RFA direct costs were $9,373 with 4.54 life years obtained, while direct costs for TACE were $15,791 with 1.87 life years obtained. Results from the model were not sensitive to any estimated component. Conclusions: Identifying direct costs and overall effects of non-surgical therapies are important factors to consider in managing HCC. Our analysis indicates that RFA is the most cost-effective strategy across all ranges of direct costs when compared to TACE. While RFA had a wider range of direct costs, results from the Markov model demonstrate that RFA is more cost-effective than TACE for any plausible range of estimates for cost and tumor progression. Future randomized controlled trials are needed to compare CE of all non-surgical therapies for HCC.

W1774 Cost Effectiveness of Radiofrequency Ablation Versus Transcatheter Arterial Chemoembolization in Patients with Hepatocellular Carcinoma Less Than 4.5 CM in Diameter

Background: While 5 year survival and tumor progression after radiofrequency ablation (RFA) and transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) have been studied, data on cost-effectiveness (CE) comparing these 2 procedures are lacking. Using Markov models, we assessed whether RFA or TACE was more costeffective. Methods: Clinical and financial data were obtained for RFA or TACE patients from June 2006 June 2008. Patient's age, gender, tumor size, treatment course, and direct costs were recorded. Costs of complications were excluded when entering direct procedure costs into the model. Probabilities of tumor progression after RFA or TACE were obtained from published studies. Data was analyzed using TreeAge Pro 2008 Suite 1.2 (TreeAge Software Inc, Williamstown, MA). A Markov model was developed to compare costs and survival outcomes over 5 years, and sensitivity analyses assessed whether model results were stable within plausible ranges of the estimated components. Results: 95 patients were evaluated, 16 received RFA (age = 62.5 ± 11.4 yrs; 10M), and 79 received TACE (age = 64.4 ± 10.6 yrs; 58M). Average tumor size for RFA was 2.23 x 1.84 cm ± 0.96 x 0.83 cm, while for TACE was 3.02 x 2.43 cm ± 1.38 x 1.31 cm. The baseline estimate of the probability of tumor progression after RFA was 0.056 (range = 0.036-0.06) and with TACE was 0.43 (range = 0.19-0.68). Average cost of RFA is $3133 (range=$1760 to $8063) while TACE is $6828 (range=$6687 to $7132). The incremental cost-effectiveness ratio average is $2908 (range= $2086 to $3730). Over 5 years, RFA direct costs were $9,373 with 4.54 life years obtained, while direct costs for TACE were $15,791 with 1.87 life years obtained. Results from the model were not sensitive to any estimated component. Conclusions: Identifying direct costs and overall effects of non-surgical therapies are important factors to consider in managing HCC. Our analysis indicates that RFA is the most cost-effective strategy across all ranges of direct costs when compared to TACE. While RFA had a wider range of direct costs, results from the Markov model demonstrate that RFA is more cost-effective than TACE for any plausible range of estimates for cost and tumor progression. Future randomized controlled trials are needed to compare CE of all non-surgical therapies for HCC.

W1776 Development and Evaluation of Gold Nanoparticle Based Laser Nano Thermolysis As a Potential New Active Intervention: A Novel Therapeutic Approach to Hepatocellular Cancer

Background: While 5 year survival and tumor progression after radiofrequency ablation (RFA) and transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) have been studied, data on cost-effectiveness (CE) comparing these 2 procedures are lacking. Using Markov models, we assessed whether RFA or TACE was more costeffective. Methods: Clinical and financial data were obtained for RFA or TACE patients from June 2006 June 2008. Patient's age, gender, tumor size, treatment course, and direct costs were recorded. Costs of complications were excluded when entering direct procedure costs into the model. Probabilities of tumor progression after RFA or TACE were obtained from published studies. Data was analyzed using TreeAge Pro 2008 Suite 1.2 (TreeAge Software Inc, Williamstown, MA). A Markov model was developed to compare costs and survival outcomes over 5 years, and sensitivity analyses assessed whether model results were stable within plausible ranges of the estimated components. Results: 95 patients were evaluated, 16 received RFA (age = 62.5 ± 11.4 yrs; 10M), and 79 received TACE (age = 64.4 ± 10.6 yrs; 58M). Average tumor size for RFA was 2.23 x 1.84 cm ± 0.96 x 0.83 cm, while for TACE was 3.02 x 2.43 cm ± 1.38 x 1.31 cm. The baseline estimate of the probability of tumor progression after RFA was 0.056 (range = 0.036-0.06) and with TACE was 0.43 (range = 0.19-0.68). Average cost of RFA is $3133 (range=$1760 to $8063) while TACE is $6828 (range=$6687 to $7132). The incremental cost-effectiveness ratio average is $2908 (range= $2086 to $3730). Over 5 years, RFA direct costs were $9,373 with 4.54 life years obtained, while direct costs for TACE were $15,791 with 1.87 life years obtained. Results from the model were not sensitive to any estimated component. Conclusions: Identifying direct costs and overall effects of non-surgical therapies are important factors to consider in managing HCC. Our analysis indicates that RFA is the most cost-effective strategy across all ranges of direct costs when compared to TACE. While RFA had a wider range of direct costs, results from the Markov model demonstrate that RFA is more cost-effective than TACE for any plausible range of estimates for cost and tumor progression. Future randomized controlled trials are needed to compare CE of all non-surgical therapies for HCC.